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A randomized, double-blind trial on the effect of treatment with montelukast, budesonide, montelukast with budesonide, formoterol with budesonide on lung function and clinical symptoms in children with asthma
Abstracts S151
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
Short-Term and Long-Term Asthma Control in Patients With Mild Persistent Asthma Receiving Montelukast or Fluticasone: A Randomized Controlled Trial R. S. Zeiger1, J. M. Edelman2, S. R. Bird2, M. S. Kaplan1, M. Schatz1, D. S. Pearlman3, E. J. Orav4, C. M. Hustad2; 1Kaiser Permanente, San Diego, CA, 2Merck & Co., Inc., West Point, PA, 3Colorado Allergy and Asthma Centers, PC, Denver, CO, 4Brigham and Women’s Hospital, Boston, MA. RATIONALE: To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescuefree days (RFD). METHODS: Participants 15 to 85 years old with mild persistent asthma (n=400) were randomized into a year-long, parallel-group, multicenter study with a 12-week, double-blind period of oral montelukast (10mg once nightly) or inhaled fluticasone (88g twice daily), followed by a 36week, open-label period. RESULTS: The mean percentage of RFD was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% CI: 3.2%, 6.8%), but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8%, 11.7%). Both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, but greater improvements occurred with fluticasone in lung function (both periods) and asthma control (open-label period). Post-hoc analyses revealed a difference in RFD favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline. No differences were detected in the remaining quartiles. CONCLUSION: In individuals with mild persistent asthma, RFD and most other asthma control measures, except for lung function, improved similarly with both fluticasone and montelukast over the short-term. With more prolonged open-label treatment, asthma control improved more with fluticasone. Fluticasone appeared to be better for those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that the classification scheme for mild persistent asthma may need to be re-evaluated. Funding: Merck & Co., Inc.
601
A Randomized, Double-Blind Trial on the Effect of Treatment With Montelukast, Budesonide, Montelukast With Budesonide, Formoterol With Budesonide on Lung Function and Clinical Symptoms in Children With Asthma I. Stelmach1, T. Grzelewski1, J. Jerzynska1, P. Kuna2; 1Dep. of Pediatrics and Allergy, M Curie Hospital, Zgierz, POLAND, 2Dep. of Allergy and Pneumonology, Medical University of Lodz, Lodz, POLAND. RATIONALE: The purpose of this study was to define the effect of treatment with montelukast , budesonide, montelukast with budesonide, formoterol with budesonide on lung function (FEV1, specific airway resistance (sRaw), resistance measured by the interrupter technique (Rint)) and clinical symptoms (symptoms score ) in children with mild to moderate asthma. METHODS: An 4-week, randomized, double-blind trial was carried out. The subjects were 80 children 6-16 years old with mild-to-moderate atopic asthma, who were allergic to dust mite. Patients were randomly allocated to receive 5 or 10 mg (according to age) montelukast (M) (n =
602
20), 200 mcg budesonide (B) (n=20), 5 or 10 mg (according to age) M with 200 mcg B (n=20), 4,5 mcg formoterol (F) with 200 mcg B (n=20) for 4 weeks. RESULTS: Symptoms score improved significantly after treatment in all groups: M (p<0,0001), B (p=0,011), M with B (p<0,001), F with B (p<0,0001). FEV1 and sRaw values did not differ significantly after treatment in any group. Mean values of Rint (% of predicted value) before and after treatment in M with B group were 138,2±21,8 and 123,2±19,9 respectively (p=0,02). Rint values did not differ significantly after treatment in any other group. CONCLUSIONS: Clinical symptoms improved significantly in all treatment groups. Additionaly montelukast in combination with budesonide significantly decreased Rint which is important parameter of airway obstruction. This observation raises the possibility that montelukast, combined with budesonide, may be optimal treatment combination reducing airway obstruction in children with asthma. Phase I Study of MN-001, an Oral Anti-inflammatory Agent for the Treatment of Asthma K. W. Locke; MediciNova, Inc., San Diego, CA. RATIONALE: A variety of inflammatory mechanisms are involved in the pathogenesis of asthma. MN-001 blocks a number of these mechanisms in vitro, including leukotriene receptors, phosphodiesterases III and IV, 5-lipoxygenase, phospholipase C and thromboxane A2. MN-001 is also active in a variety of in vivo preclinical asthma models. Extensive preclinical toxicology testing has demonstrated that MN-001 has a relatively low toxicity. Therefore, it was essential to evaluate the clinical safety and pharmacokinetics of MN-001 to guide design of efficacy trials. METHODS: MN-001 (250, 500, 750 or 1000 mg BID) was evaluated in a multiple-dose, double-blind, placebo-controlled, ascending-dose tolerance study in 32 healthy human volunteers. RESULTS: MN-001 was well tolerated at oral doses up to 1000 mg BID for 7 days. The adverse effects (e.g., upper abdominal pain, loose stools and nausea) of MN-001 were mild in intensity and short in duration. There were no dose-related toxicities identified in this study. MN-001 was rapidly absorbed and exhibited linear pharmacokinetics following singleand multiple-dose administrations of the same dose level from 250 to 1000 mg BID. CONCLUSIONS: MN-001 was well tolerated when administered orally to human volunteers at doses up to 1000 mg BID for 7 days.
603
Ketokonazol Treatment Prevents the Progress of “Allergic March” in Children With Atopic Dermatitis—Prospective Studies A. M. Hofman, T. Hofman; Center of Allergology, Poznan, POLAND. RATIONALE: The aim of this study was to estimate the influence of ketokonazol treatment on evolution of “atopic march” in children with atopic dermatitis (AD). METHODS: 97 children aged up to 24 months of life with AD were examined. They were on constant observation up to 12 year of life. In 4th year of life patients were devided into 2 groups: one-53 children had additional treatment by ketokonazol (taken periodically) and diet without sugar ( K+ group), and second- 36 children without this treatment ( Kgroup). RESULTS: In 1st year of life 9,3 % of children suffered also from bronchial asthma (BA), and 4,1 % had inhalant allergy. In 4th year of life BA occurred in 16,8% children from K+ group, and 13,8 % from Kgroup. And inhalant allergy was observed in 7,5% K+ and 8,4% K-. In children aged 8 in K+ group BA occurred in 26,4%, however in K- in 33,3%. And inhalant allergy similar in 26,4% K+ and 33,3% K-. In 12 year of life BA decreased to 11,3% in K+ group, but increased to 41,6% in K- group. The same percent was noted due to inhalant allergy- 11,3% in K+ and 44,4% in K- group. Moreover, in K- group also venom allergy occurred, which was not met in K+ group. CONCLUSIONS: Ketokonazol treatment in children with AD prevents development of “ allergic march”, BA and inhalant allergy.
604
MONDAY
ed in a significant improvement from baseline in daytime asthma symptom score (0.54 vs. 0.34, p=0.002; least-squares mean difference: 0.20 [0.34, 0.07]) and a reduction in daily puffs of -agonist (0.83 vs. 0.42, p = 0.003; least-squares mean difference: 0.41 [0.67, 0.14]). Few patients discontinued the study due to asthma (M:1.3% vs. P:3.1%), and there was no significant difference between treatment groups in the number of patients experiencing an asthma attack. CONCLUSIONS: In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast provided significant asthma symptom relief over a 3-week treatment period during allergy season when compared to placebo. Funding: Merck & Co., Inc.
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
Short-Term and Long-Term Asthma Control in Patients With Mild Persistent Asthma Receiving Montelukast or Fluticasone: A Randomized Controlled Trial R. S. Zeiger1, J. M. Edelman2, S. R. Bird2, M. S. Kaplan1, M. Schatz1, D. S. Pearlman3, E. J. Orav4, C. M. Hustad2; 1Kaiser Permanente, San Diego, CA, 2Merck & Co., Inc., West Point, PA, 3Colorado Allergy and Asthma Centers, PC, Denver, CO, 4Brigham and Women’s Hospital, Boston, MA. RATIONALE: To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescuefree days (RFD). METHODS: Participants 15 to 85 years old with mild persistent asthma (n=400) were randomized into a year-long, parallel-group, multicenter study with a 12-week, double-blind period of oral montelukast (10mg once nightly) or inhaled fluticasone (88g twice daily), followed by a 36week, open-label period. RESULTS: The mean percentage of RFD was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% CI: 3.2%, 6.8%), but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8%, 11.7%). Both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, but greater improvements occurred with fluticasone in lung function (both periods) and asthma control (open-label period). Post-hoc analyses revealed a difference in RFD favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline. No differences were detected in the remaining quartiles. CONCLUSION: In individuals with mild persistent asthma, RFD and most other asthma control measures, except for lung function, improved similarly with both fluticasone and montelukast over the short-term. With more prolonged open-label treatment, asthma control improved more with fluticasone. Fluticasone appeared to be better for those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that the classification scheme for mild persistent asthma may need to be re-evaluated. Funding: Merck & Co., Inc.
601
A Randomized, Double-Blind Trial on the Effect of Treatment With Montelukast, Budesonide, Montelukast With Budesonide, Formoterol With Budesonide on Lung Function and Clinical Symptoms in Children With Asthma I. Stelmach1, T. Grzelewski1, J. Jerzynska1, P. Kuna2; 1Dep. of Pediatrics and Allergy, M Curie Hospital, Zgierz, POLAND, 2Dep. of Allergy and Pneumonology, Medical University of Lodz, Lodz, POLAND. RATIONALE: The purpose of this study was to define the effect of treatment with montelukast , budesonide, montelukast with budesonide, formoterol with budesonide on lung function (FEV1, specific airway resistance (sRaw), resistance measured by the interrupter technique (Rint)) and clinical symptoms (symptoms score ) in children with mild to moderate asthma. METHODS: An 4-week, randomized, double-blind trial was carried out. The subjects were 80 children 6-16 years old with mild-to-moderate atopic asthma, who were allergic to dust mite. Patients were randomly allocated to receive 5 or 10 mg (according to age) montelukast (M) (n =
602
20), 200 mcg budesonide (B) (n=20), 5 or 10 mg (according to age) M with 200 mcg B (n=20), 4,5 mcg formoterol (F) with 200 mcg B (n=20) for 4 weeks. RESULTS: Symptoms score improved significantly after treatment in all groups: M (p<0,0001), B (p=0,011), M with B (p<0,001), F with B (p<0,0001). FEV1 and sRaw values did not differ significantly after treatment in any group. Mean values of Rint (% of predicted value) before and after treatment in M with B group were 138,2±21,8 and 123,2±19,9 respectively (p=0,02). Rint values did not differ significantly after treatment in any other group. CONCLUSIONS: Clinical symptoms improved significantly in all treatment groups. Additionaly montelukast in combination with budesonide significantly decreased Rint which is important parameter of airway obstruction. This observation raises the possibility that montelukast, combined with budesonide, may be optimal treatment combination reducing airway obstruction in children with asthma. Phase I Study of MN-001, an Oral Anti-inflammatory Agent for the Treatment of Asthma K. W. Locke; MediciNova, Inc., San Diego, CA. RATIONALE: A variety of inflammatory mechanisms are involved in the pathogenesis of asthma. MN-001 blocks a number of these mechanisms in vitro, including leukotriene receptors, phosphodiesterases III and IV, 5-lipoxygenase, phospholipase C and thromboxane A2. MN-001 is also active in a variety of in vivo preclinical asthma models. Extensive preclinical toxicology testing has demonstrated that MN-001 has a relatively low toxicity. Therefore, it was essential to evaluate the clinical safety and pharmacokinetics of MN-001 to guide design of efficacy trials. METHODS: MN-001 (250, 500, 750 or 1000 mg BID) was evaluated in a multiple-dose, double-blind, placebo-controlled, ascending-dose tolerance study in 32 healthy human volunteers. RESULTS: MN-001 was well tolerated at oral doses up to 1000 mg BID for 7 days. The adverse effects (e.g., upper abdominal pain, loose stools and nausea) of MN-001 were mild in intensity and short in duration. There were no dose-related toxicities identified in this study. MN-001 was rapidly absorbed and exhibited linear pharmacokinetics following singleand multiple-dose administrations of the same dose level from 250 to 1000 mg BID. CONCLUSIONS: MN-001 was well tolerated when administered orally to human volunteers at doses up to 1000 mg BID for 7 days.
603
Ketokonazol Treatment Prevents the Progress of “Allergic March” in Children With Atopic Dermatitis—Prospective Studies A. M. Hofman, T. Hofman; Center of Allergology, Poznan, POLAND. RATIONALE: The aim of this study was to estimate the influence of ketokonazol treatment on evolution of “atopic march” in children with atopic dermatitis (AD). METHODS: 97 children aged up to 24 months of life with AD were examined. They were on constant observation up to 12 year of life. In 4th year of life patients were devided into 2 groups: one-53 children had additional treatment by ketokonazol (taken periodically) and diet without sugar ( K+ group), and second- 36 children without this treatment ( Kgroup). RESULTS: In 1st year of life 9,3 % of children suffered also from bronchial asthma (BA), and 4,1 % had inhalant allergy. In 4th year of life BA occurred in 16,8% children from K+ group, and 13,8 % from Kgroup. And inhalant allergy was observed in 7,5% K+ and 8,4% K-. In children aged 8 in K+ group BA occurred in 26,4%, however in K- in 33,3%. And inhalant allergy similar in 26,4% K+ and 33,3% K-. In 12 year of life BA decreased to 11,3% in K+ group, but increased to 41,6% in K- group. The same percent was noted due to inhalant allergy- 11,3% in K+ and 44,4% in K- group. Moreover, in K- group also venom allergy occurred, which was not met in K+ group. CONCLUSIONS: Ketokonazol treatment in children with AD prevents development of “ allergic march”, BA and inhalant allergy.
604
MONDAY
ed in a significant improvement from baseline in daytime asthma symptom score (0.54 vs. 0.34, p=0.002; least-squares mean difference: 0.20 [0.34, 0.07]) and a reduction in daily puffs of -agonist (0.83 vs. 0.42, p = 0.003; least-squares mean difference: 0.41 [0.67, 0.14]). Few patients discontinued the study due to asthma (M:1.3% vs. P:3.1%), and there was no significant difference between treatment groups in the number of patients experiencing an asthma attack. CONCLUSIONS: In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast provided significant asthma symptom relief over a 3-week treatment period during allergy season when compared to placebo. Funding: Merck & Co., Inc.